同时性多原发肺腺癌组织编码转录因子ERG基因相同位点突变1例报告

Concordant point mutation of ETS-related gene(ERG)in tumor tissues from a synchronous multiple primary lung cancer:A case report

E26转录因子(E26 transformation-specific,ETS)相关基因(ETS-related gene,ERG)是一种细胞生长调控基因,其与跨膜丝氨酸蛋白酶2基因(transmembrane serine protease 2,TMPRSS2)融合并重新排列,在前列腺癌发生中发挥关键作用[1-2]。最近的一项研究尝试采用大分子多肽靶向ERG,通过破坏其功能,用于治疗前列腺癌[3],但较少见ERG在肺癌组织中表达和突变的报道。本研究报道了1例术后确诊的同时性多原发肺癌(synchronous multiple primary lung cancer,SMPLC)患者,通过Illumina高通量测序平台对各癌组织及其癌旁组织的315个基因组合(panel)进行分析,发现在双侧肺癌组织中ERG相同位点存在高突变频率,并探讨其可能存在的临床价值。

The rearrangement of the gene encoding the transcription factor ETS-related gene(ERG)is thought to play a key role in the development of prostate cancer.However,the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma(NSCLC).Here,we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs.The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography(CT)scan.After conducting lobectomies at the both lungs,the tumor nodules were all removed,and the histological analysis suggested adenocarcinoma at the both tumor lesions.The patient was diagnosed with synchronous multiple primary lung cancer(SMPLC)based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines.An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC.Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score.The read depth was≥1000×and the depth of coverage was 95%.The data revealed a discordant epidermal growth factor receptor(EGFR)from the separate lungs;additionally,a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions.This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC.This study suggests that the same environment may contribute certain gene(s)mutations in the same sites in the early stages of polyclonal tumor origins;meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.